Growth Regulation of HPV-Positive Keratinocytes by TGF-βl

Abstract

Human papillomaviruses (HPV) are eptheliotropic DNA viruses, some of which have been implicated in the development of cervical cancer (1). Despite intensive research, little is known about the molecular and cellular events in cervical carcinogenesis, in large part because of the lack of in vitro models for HPV infection. Although it is still not possible to propagate human papillomaviruses in tissue culture, immortalized cell lines which constitutively express the E6 and E7 transforming proteins of two ‘high risk’ HPVs, HPV 16 and HPV 18, have recently been established in several laboratories by transfection of HPV DNA into foreskin and cervical keratinocytes (2). Such cell lines contain transcriptionally active HPV sequences, display variable patterns of keratinocyte differentiation in monolayer culture, and produce epithelium morphologically indistinguishable from cervical intraepithelial neoplasia when grown on three-dimensional collagen/fibroblast rafts (3). Thus, the availability of HPV-positive cell lines with many phenotypic similarities to HPV-induced lesions in vivo represents a significant advance for mechanistic studies of the transformation events triggered by HPV infection.